The immunologic disorders, idiopathic thrombocytopenic purpura (ITP), neonatal (INT)-post-transfusion (PTP) and drug-purpura account for the majority of clinical thrombocytopenias of immune origin. The antibody reactions involved in these disorders are relevant to understanding autoimmunity, histocompatibility, malignant surveillance, isoimmune reactions, disorders due to antigen-antibody complexes and cellular immune injury generally. We have developed more precise and sensitive assays for cell-associated IgG, IgM, IgA and albumin than heretofore available and found that immune injury by specific antibody causes platelets to associate with all classes of immunoglobulins and with other serum proteins. By electronmicroscopy this association appears to result from trapping of plasma protein by resealed cytoplasmic-free platelet membranes. An animal model for ITP was developed that duplicated the cellular and immunologic abnormalities of this disease. Three additional cases of PTP were found to be due to isoantibodies against previously unrecognized platelet antigen specificities. We have extensively determined the molecular characteristics of one of these determinants. Nitrocellulose transfer techniques and a precipitin test utilizing labeled platelet proteins were used to detect antiplatelet antibodies of INT and PTP more sensitively, specifically and easily than previously possible. Platelet membrane receptor glycoproteins were purified as reactants in diagnostic tests for isoantibodies, and drug antibodies. We found that the Fab portion of drug antibodies is responsible for their attachment to platelet and red cell surfaces, correcting erroneous reports that the Fc portion is responsible. Association constants of drug-antibody reactions with platelets and red cells have been established by saturation kinetics and equilibrium dialysis, and the red cell receptor for a tolmetin-dependent hemolytic antibody was found to be the band 3 anion channel protein. Utilizing antibodies from patients that reacted specifically with platelet glycoprotein I, IIb or IIIa, bone marrow megakarycyte progenitors were detected by immunofluorescence before cells could be differentiated morphologically.